title: Surface-expressed viral proteins in feline infectious peritonitis virus-infected monocytes are internalized through a clathrin- and caveolae-independent pathway.
abstract: Infection with feline infectious peritonitis virus (FIPV), a feline coronavirus, frequently leads to death in spite of a strong humoral immune response. In previous work, we reported that infected monocytes, the in vivo target cells of FIPV, express viral proteins in their plasma membranes. These proteins are quickly internalized upon binding of antibodies. As the cell surface is cleared from viral proteins, internalization might offer protection against antibody-dependent cell lysis. Here, the internalization and subsequent trafficking of the antigen-antibody complexes were characterized using biochemical, cell biological and genetic approaches. Internalization occurred through a clathrin- and caveolae-independent pathway that did not require dynamin, rafts, actin or rho-GTPases. These findings indicate that the viral antigen-antibody complexes were not internalized through any of the previously described pathways. Further characterization showed that this internalization process was independent from phosphatases and tyrosine kinases but did depend on serine/threonine kinases. After internalization, the viral antigen-antibody complexes passed through the early endosomes, where they resided only briefly, and accumulated in the late endosomes. Between 30 and 60 min after antibody addition, the complexes left the late endosomes but were not degraded in the lysosomes. This study reveals what is probably a new internalization pathway into primary monocytes, confirming once more the complexity of endocytic processes.
authors.affiliation: Laboratory of Virology, Faculty of Veterinary Medicine, Ghent University, Belgium.
authors.forename: Hannah L
authors.initials: HL
authors.lastname: Dewerchin
authors.affiliation: Laboratory of Virology, Faculty of Veterinary Medicine, Ghent University, Belgium.
authors.forename: Els
authors.initials: E
authors.lastname: Cornelissen
authors.affiliation: Laboratory of Virology, Faculty of Veterinary Medicine, Ghent University, Belgium.
authors.forename: Evelien
authors.initials: E
authors.lastname: Van Hamme
authors.affiliation: Department of Clinical Chemistry, Microbiology and Immunology, Faculty of Medicine and Health Science, Ghent University, Belgium.
authors.forename: Kaatje
authors.initials: K
authors.lastname: Smits
authors.affiliation: Department of Clinical Chemistry, Microbiology and Immunology, Faculty of Medicine and Health Science, Ghent University, Belgium.
authors.forename: Bruno
authors.initials: B
authors.lastname: Verhasselt
authors.affiliation: Laboratory of Virology, Faculty of Veterinary Medicine, Ghent University, Belgium.
authors.forename: Hans J
authors.initials: HJ
authors.lastname: Nauwynck
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D000956:Antigens, Viral / Q000276:immunology; D002415:Cats; D021941:Caveolae / Q000502:physiology* / Q000821:virology; D002966:Clathrin / Q000502:physiology*; D016765:Coronavirus, Feline / Q000276:immunology / Q000502:physiology*; D011992:Endosomes / Q000276:immunology / Q000821:virology; D016766:Feline Infectious Peritonitis / Q000276:immunology / Q000503:physiopathology*; D017930:Genes, Reporter; D008954:Models, Biological; D009000:Monocytes / Q000821:virology; D010957:Plasmids; D014764:Viral Proteins / Q000096:biosynthesis*; D053586:Virus Internalization
chemical_list: D000914:Antibodies, Viral; D000956:Antigens, Viral; D002966:Clathrin; D014764:Viral Proteins